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. 1998 Aug;43(2):272–279. doi: 10.1136/gut.43.2.272

Hepatosplanchnic haemodynamics and renal blood flow and function in rats with liver failure

P Javle 1, J Yates 1, H Kynaston 1, K Parsons 1, S Jenkins 1
PMCID: PMC1727229  PMID: 10189857

Abstract

Background—Massive liver necrosis, characteristic of acute liver failure, may affect hepatosplanchnic haemodynamics, and contribute to the alterations in renal haemodynamics and function. 
Aims—To investigate the relation between hepatosplanchnic haemodynamics, including portal systemic shunting, and renal blood flow and function in rats with acute liver failure. 
Methods—Liver failure was induced in male Wistar rats by intraperitoneal injection of 1.1 g/kg of D(+)-galactosamine hydrochloride. The parameters assessed included: systemic, hepatosplanchnic, and renal blood flow (57Co microsphere method); portal-systemic shunting and intrarenal shunting (consecutive intrasplenic, intraportal, or renal arterial injections of 99mTc methylene diphosphonate and 99mTc albumin microspheres); arterial blood pressure and portal pressure; renal function; and liver function (liver function tests and 14C aminopyrine breath test). 
Results—Progressive liver dysfuntion was accompanied by the development of a hyperdynamic circulation, a highly significant decrease in renal blood flow and function, and an increase in intrarenal shunting 36, 42, and 48 hours after administration of D-galactosamine. The alterations in renal blood flow and function were accompanied by significant increases in portal pressure, portal venous inflow, and intrahepatic portal systemic shunting in galactosamine treated rats compared with controls. There was a significant correlation between changes in renal blood flow and changes in portal pressure, intrahepatic portal systemic shunting, and deterioration in liver function (r=0.8, p<0.0001). 
Conclusions—The results of this study suggest that both increased intrahepatic portal systemic shunting and hepatocyte impairment may contribute to alterations in renal haemodynamics and function. 



Keywords: liver failure; hepatosplanchnic; systemic; renal; haemodynamics

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Figure 1 .

Figure 1

Changes in circulatory and renal haemodynamics after injection of D-galactosamine or saline. Results are expressed as mean (SEM). **p<0.01, ***p<0.001.

Figure 2 .

Figure 2

Changes in hepatosplanchnic haemodynamics after injection of D-galactosamine or saline. Results are expressed as mean (SEM). **p<0.01.

Figure 3 .

Figure 3

Changes in intrahepatic portal-systemic shunting after injection of D-galactosamine or saline. Results are expressed as mean (SEM). ***p<0.001.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson R. J., Cronin R. E., McDonald K. M., Schrier R. W. Mechanisms of portal hypertension-induced alterations in renal hemodynamics, renal water excretion, and renin secretion. J Clin Invest. 1976 Oct;58(4):964–970. doi: 10.1172/JCI108550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Benoit J. N., Granger D. N. Splanchnic hemodynamics in chronic portal hypertension. Semin Liver Dis. 1986 Nov;6(4):287–298. doi: 10.1055/s-2008-1040611. [DOI] [PubMed] [Google Scholar]
  3. Bihari D. J., Gimson A. E., Williams R. Cardiovascular, pulmonary and renal complications of fulminant hepatic failure. Semin Liver Dis. 1986 May;6(2):119–128. doi: 10.1055/s-2008-1040595. [DOI] [PubMed] [Google Scholar]
  4. Bihari D., Gimson A. E., Waterson M., Williams R. Tissue hypoxia during fulminant hepatic failure. Crit Care Med. 1985 Dec;13(12):1034–1039. doi: 10.1097/00003246-198512000-00010. [DOI] [PubMed] [Google Scholar]
  5. Chirito E., Lister C., Chang T. M. Biochemical, hematological and histological changes in a fulminant hepatic failure rat model for artificial liver assessment. Artif Organs. 1979 Feb;3(1):42–46. doi: 10.1111/j.1525-1594.1979.tb03804.x. [DOI] [PubMed] [Google Scholar]
  6. Decker K., Keppler D. Galactosamine induced liver injury. Prog Liver Dis. 1972;4:183–199. [PubMed] [Google Scholar]
  7. Desmond P. V., James R., Schenker S., Gerkens J. F., Branch R. A. Preservation of glucuronidation in carbon tetrachloride-induced acute liver injury in the rat. Biochem Pharmacol. 1981 May 1;30(9):993–999. doi: 10.1016/0006-2952(81)90045-9. [DOI] [PubMed] [Google Scholar]
  8. Epstein M., Berk D. P., Hollenberg N. K., Adams D. F., Chalmers T. C., Abrams H. L., Merrill J. P. Renal failure in the patient with cirrhosis. The role of active vasoconstriction. Am J Med. 1970 Aug;49(2):175–185. doi: 10.1016/s0002-9343(70)80073-0. [DOI] [PubMed] [Google Scholar]
  9. Epstein M., Schneider N., Befeler B. Relationship of systemic and intrarenal hemodynamics in cirrhosis. J Lab Clin Med. 1977 Jun;89(6):1175–1187. [PubMed] [Google Scholar]
  10. Guarner F., Hughes R. D., Gimson A. E., Williams R. Renal function in fulminant hepatic failure: haemodynamics and renal prostaglandins. Gut. 1987 Dec;28(12):1643–1647. doi: 10.1136/gut.28.12.1643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Guarner F., Hughes R. D., Gimson A. E., Williams R. Renal function in fulminant hepatic failure: haemodynamics and renal prostaglandins. Gut. 1987 Dec;28(12):1643–1647. doi: 10.1136/gut.28.12.1643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. HECKER R., SHERLOCK S. Electrolyte and circulatory changes in terminal liver failure. Lancet. 1956 Dec 1;271(6953):1121–1125. doi: 10.1016/s0140-6736(56)90149-0. [DOI] [PubMed] [Google Scholar]
  13. Hepner G. W., Vesell E. S. Assessment of aminopyrine metabolism in man by breath analysis after oral administration of 14C-aminopyrine. Effects of phenobarbital, disulfiram and portal cirrhosis. N Engl J Med. 1974 Dec 26;291(26):1384–1388. doi: 10.1056/NEJM197412262912605. [DOI] [PubMed] [Google Scholar]
  14. Hörtnagl H., Singer E. A., Lenz K., Kleinberger G., Lochs H. Substance P is markedly increased in plasma of patients with hepatic coma. Lancet. 1984 Mar 3;1(8375):480–483. doi: 10.1016/s0140-6736(84)92851-4. [DOI] [PubMed] [Google Scholar]
  15. Kew M. C., Brunt P. W., Varma R. R., Hourigan K. J., Williams H. S., Sherlock S. Renal and intrarenal blood-flow in cirrhosis of the liver. Lancet. 1971 Sep 4;2(7723):504–510. doi: 10.1016/s0140-6736(71)90435-1. [DOI] [PubMed] [Google Scholar]
  16. Lang F., Gerok W., Häussinger D. New clues to the pathophysiology of hepatorenal failure. Clin Investig. 1993 Feb;71(2):93–97. doi: 10.1007/BF00179987. [DOI] [PubMed] [Google Scholar]
  17. McDevitt D. G., Nies A. S. Simultaneous measurement of cardiac output and its distribution with microspheres in the rat. Cardiovasc Res. 1976 Jul;10(4):494–498. doi: 10.1093/cvr/10.4.494. [DOI] [PubMed] [Google Scholar]
  18. Moore K., Ward P. S., Taylor G. W., Williams R. Systemic and renal production of thromboxane A2 and prostacyclin in decompensated liver disease and hepatorenal syndrome. Gastroenterology. 1991 Apr;100(4):1069–1077. doi: 10.1016/0016-5085(91)90284-r. [DOI] [PubMed] [Google Scholar]
  19. Reichen J., Arts B., Schafroth U., Zimmermann A., Zeltner B., Zysset T. Aminopyrine N-demethylation by rats with liver cirrhosis. Evidence for the intact cell hypothesis. A morphometric-functional study. Gastroenterology. 1987 Oct;93(4):719–726. doi: 10.1016/0016-5085(87)90433-1. [DOI] [PubMed] [Google Scholar]
  20. Ring-Larsen H., Hesse B., Stigsby B. Effect of portal-systemic anastomosis on renal haemodynamics in cirrhosis. Gut. 1976 Nov;17(11):856–860. doi: 10.1136/gut.17.11.856. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ring-Larsen H., Palazzo U. Renal failure in fulminant hepatic failure and terminal cirrhosis: a comparison between incidence, types, and prognosis. Gut. 1981 Jul;22(7):585–591. doi: 10.1136/gut.22.7.585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Schelling J. R., Linas S. L. Hepatorenal syndrome. Semin Nephrol. 1990 Nov;10(6):565–570. [PubMed] [Google Scholar]
  23. Schumacker P. T., Cain S. M. The concept of a critical oxygen delivery. Intensive Care Med. 1987;13(4):223–229. doi: 10.1007/BF00265110. [DOI] [PubMed] [Google Scholar]
  24. Sherlock S. Vasodilatation associated with hepatocellular disease: relation to functional organ failure. Gut. 1990 Apr;31(4):365–367. doi: 10.1136/gut.31.4.365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Shoemaker W. C., Appel P. L., Kram H. B. Hemodynamic and oxygen transport effects of dobutamine in critically ill general surgical patients. Crit Care Med. 1986 Dec;14(12):1032–1037. doi: 10.1097/00003246-198612000-00008. [DOI] [PubMed] [Google Scholar]
  26. Wensing G., Branch R. A. Phenobarbital influences the development of sodium retention in liver disease induced by bile duct ligation in the rat. Hepatology. 1990 May;11(5):773–778. doi: 10.1002/hep.1840110510. [DOI] [PubMed] [Google Scholar]
  27. Wensing G., Sabra R., Branch R. A. Renal and systemic hemodynamics in experimental cirrhosis in rats: relation to hepatic function. Hepatology. 1990 Jul;12(1):13–19. doi: 10.1002/hep.1840120104. [DOI] [PubMed] [Google Scholar]
  28. Wensing G., Sabra R., Branch R. A. The onset of sodium retention in experimental cirrhosis in rats is related to a critical threshold of liver function. Hepatology. 1990 May;11(5):779–786. doi: 10.1002/hep.1840110511. [DOI] [PubMed] [Google Scholar]
  29. Wilkinson S. P., Arroyo V. A., Moodie H., Blendis L. M., Williams R. Abnormalities of sodium excretion and other disorders of renal function in fulminant hepatic failure. Gut. 1976 Jul;17(7):501–505. doi: 10.1136/gut.17.7.501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Wilkinson S. P., Arroyo V. A., Moodie H., Blendis L. M., Williams R. Abnormalities of sodium excretion and other disorders of renal function in fulminant hepatic failure. Gut. 1976 Jul;17(7):501–505. doi: 10.1136/gut.17.7.501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Wilkinson S. P., Arroyo V., Gazzard B. G., Moodie H., Williams R. Relation of renal impairment and haemorrhagic diathesis to endotoxaemia in fulminant hepatic failure. Lancet. 1974 Mar 30;1(7857):521–524. doi: 10.1016/s0140-6736(74)92711-1. [DOI] [PubMed] [Google Scholar]
  32. Wilkinson S. P., Blendis L. M., Williams R. Frequency and type of renal and electrolyte disorders in fulminant hepatic failure. Br Med J. 1974 Feb 2;1(5900):186–189. doi: 10.1136/bmj.1.5900.186. [DOI] [PMC free article] [PubMed] [Google Scholar]

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